Affinity of fentanyl and its derivatives for the σ 1 -receptor.

Fentanyl and its 11 commercially available derivatives were investigated as to their affinity for the sigma(1) receptor. The parent compound is a rather poor binder (IC50 = 4973 nM), but its close derivatives (benzylfentanyl or p-fluorofentanyl) have submicromolar affinities. Modelling provides a structural basis for the observed trends in activity.